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Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS
Wenshi He1, Max K Edney2, Simon M L Paine3
1Centre for Analytical Bioscience, Advanced Materials & Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K.
Analytical Chemistry
|March 30, 2023
Summary
Orbitrap secondary ion mass spectrometry (OrbiSIMS) revealed metabolic differences in glioblastoma (GBM) tumor regions. This technique identified key metabolites and pathways essential for GBM survival, offering new therapeutic targets.
Area of Science:
- Oncology
- Metabolomics
- Mass Spectrometry
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with poor prognosis.
- Current treatments offer limited survival benefits due to intra-tumor heterogeneity.
- A need exists for novel therapeutic strategies targeting diverse GBM cell populations.
Purpose of the Study:
- To investigate glioblastoma (GBM) metabolism within its heterogeneous microenvironment.
- To demonstrate the utility of Orbitrap secondary ion mass spectrometry (OrbiSIMS) for in situ metabolomic analysis.
- To identify metabolic differences between distinct GBM regions.
Main Methods:
- Untargeted metabolomics using OrbiSIMS on formalin-fixed paraffin-embedded GBM tissues.
- Discrimination of morphologically distinct regions: viable, necrotic, and non-cancerous.
- Metabolite identification and pathway mapping.
Main Results:
- OrbiSIMS successfully differentiated viable GBM cells from those in necrotic regions.
- Specific metabolites (cytosine, phosphate, purine, xanthine, 8-hydroxy-7-methylguanine) distinguished cell populations.
- Tryptophan metabolism was identified as crucial for GBM cell survival across regions.
Conclusions:
- OrbiSIMS is capable of analyzing GBM intra-tumor heterogeneity in situ.
- Metabolic profiling can reveal critical pathways for GBM survival.
- Findings may guide the development of therapies targeting multiple GBM subpopulations.
